Kidney stones are one of the most painful disorders to afflict humans. In the United States, urinary stone disease is a common clinical problem with a high risk of recurrence. One out of every ten Americans suffer kidney stone disease sometime during their lifetime. It is the third leading cause of hospitalization in this country and the seventh leading cause for visits to urologists. Clinical treatment of stone related disorders is estimated to cost over $2 billion per year. Current medical treatment will not dissolve symptomatic kidney stones. Since most stones will not pass out of the body spontaneously, comminution with high intensity shock waves (SWL) has become nearly a standard procedure for stones in the upper urinary tract. However, compelling clinical data now suggests that SWL may cause acute renal injury, a rise in diastolic blood pressure, a decrease in renal function, and an increase in stone recurrence. This proposal seeks an alternative to SWL for kidney stone treatment. Oral dissolution therapy of kidney stones with diuretic medicinal plants has been known for millennia by the indigenous people of America, India, and Arabia. The objective of this proposal is to place in scientific perspective the ethnopharmacological use of medicinal plants in Middle America as diuretics for the treatment of kidney stones. Numerous herbal treatments of this disease seem to cure the patients. However, little evaluation of diuretic medicinal plants has been performed using objective scientific methods and the pharmacology of their phytomedicinals is still unclear. The hypothesis is that effective medicinal plants may contain a) natural diuretics that decrease Ca ion excretion, b) organic inhibitors of CaOx (oxalate) crystallization from naturally super-saturated urine, c) Ca ion chelating agents capable to further reduce the free Ca concentration, d) amphiphilic agents or enzymes that digest the organic matrix of large stones, and e) anti-inflammatory agents and urinary muscle relaxants that facilitate the passage of smaller stones. This hypothesis will be tested by 1) clinical studies with patients treated for kidney stones in Puerto Rico, 2) physicochemical in vitro studies with medicinal plant extracts, and 3) selected in vivo tests with an animal model. The specific aims will be: a) collection and study of clinical records to find whether patients use medicinal plants to break and expel kidney stones, b) botanical identification of plants likely to posses biological activity, c) field collection of plant material, and d) characterization of plant extracts using both in vitro and in vivo models for kidney stone dissolution. Screens will be conducted with crude plant extracts to test for comminution activity against CaOx and CaP stones and low levels of free Ca ions. When crude extracts prove positive in either test, biodirected assays with animals will allow to identify active fractions with biodynamic compounds. Isolation and characterization of these principles will provide chemical which could be developed into new pharmaceutical of substantial of substantial to human health.